Abstract
BACKGROUND: While atrial fibrillation is the leading cause of cardioembolic stroke in elderly patients, the underlying cardiac substrate often remains unidentified. Transthyretin cardiac amyloidosis (ATTR-CA), a treatable cardiomyopathy affecting predominantly elderly males, causes atrial fibrillation and carries high thromboembolic risk but remains largely unrecognized among stroke physicians. With disease-modifying therapies now available, identifying ATTR-CA as a cause of cardioembolic stroke has become increasingly important. METHODS: To determine ATTR-CA prevalence and identify clinical indicators enabling systematic screening for this underdiagnosed cardiomyopathy, we performed a single-center retrospective cohort study of 143 consecutive patients with cardioembolic stroke among 430 ischemic stroke admissions. Patients with clinical suspicion underwent ⁹⁹ᵐTc-pyrophosphate scintigraphy for ATTR-CA diagnosis. RESULTS: ATTR-CA was diagnosed in 14/143 patients (9.8%; 95% confidence interval: 5.4-16.0%). Notably, 50% of patients were newly diagnosed with ATTR-CA following stroke presentation. Compared with non-CA patients (n = 129), ATTR-CA patients demonstrated: male predominance (79% vs. 49%, p = 0.048), two-fold higher levels of troponin T (median 0.058 vs. 0.029 ng/mL, p = 0.035), characteristic biventricular hypertrophy, reduced left ventricular ejection fraction, and elevated E/e' ratio. Musculoskeletal manifestations, including spinal stenosis (57%), carpal tunnel syndrome (57%), and Popeye sign (75%), were highly prevalent. CONCLUSIONS: ATTR-CA was found in nearly 10% of elderly patients with cardioembolic stroke, with half remaining undiagnosed until stroke presentation. Cardiac hypertrophy, elevated troponin levels, and musculoskeletal manifestations provide practical screening indicators for stroke physicians. Given the availability of disease-modifying therapies, these findings emphasize the importance of systematic ATTR-CA screening in cardioembolic stroke populations.